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showing the closest relationship with Sertoli cells, myoid cells, and the basement
membrane (Fig.
8.2f
). However, given that most of the spermatogonia are not stem
cells, some mechanism should provide uneven feature within the basal compart-
ment to specify the niche microenvironment for stem cells (Ogawa et al.
2005
; Hess
et al.
2006
).
8.4
Mouse Spermatogenic Stem Cells
The following is a review of the current knowledge regarding spermatogenic stem
cells in the mouse. Figure
8.3
is a schematic representation of the mouse spermato-
genic differentiation process. As mentioned above, there is no doubt that stem cells
comprise a small subset of spermatogonia among those that occupy the basal com-
partment. However, we are currently unable to identify them in the architecture of
seminiferous tubules. In the classical view known as the “A
s
model,” it has been
proposed and widely accepted that the A
s
or A
single
spermatogonia, the singly iso-
lated spermatogonia with an undifferentiated morphology, act as the stem cells (de
Rooij and Russell
2000
; Meistrich and Van Beek
1993
; Huckins
1971
; Oakberg
1971
; de Rooij
1973
). An A
s
is expected to give rise to two A
s
cells after a regular
cell division, or a pair of interconnected daughters (A
pair
or A
pr
) due to incomplete
cytokinesis. While the first division is considered to be self-renewing, the latter is
of a differentiating type (de Rooij and Russell
2000
; Meistrich and Van Beek
1993
).
A
pr
subsequently give rise to chains of 2
n
cells interconnected via intercellular
bridges, as a result of incomplete division that occurs synchronously (Russell et al.
1990
; de Rooij and Russell
2000
). According to the A
s
model, A
pr
and other inter-
connected cells are believed to be committed for differentiation and their stem cell
potential is lost.
In addition to such “morphological recognition,” function-based identifications
of stem cells have also been achieved. The first is based on posttransplantation
colony formation. Brinster and coworkers developed a transplantation technique in
which dissociated stem cells in the donor cell suspension gave rise to persisting
spermatogenic colonies after transplantation into germ-cell-depleted host testis
(Brinster and Avarbock
1994
; Brinster and Zimmermann
1994
). This was a great
breakthrough that enabled the quantitative analyses of mammalian spermatogenic
stem cells, and it is due to this system that the concentration and purification of
stem cells could be performed (Shinohara et al.
2000
). It is generally expected to
be true that the stem cells detected by transplantation are equal to the population of
A
s
. However, it is by definition impossible to evaluate this idea, unless one can
purify the A
s
and non-A
s
fractions and test their colony-formation activities.
The current consensus is that a vast majority of the stem cell activity (posttrans-
plantation colony forming activity) resides within the population of “undifferenti-
ated spermatogonia” or “A
undiff
.” A
undiff
is a collective entity originally emerged from
the morphological features that lack apparent heterochromatin condensation in
their nuclei, and includes A
s
, A
pr
, and short chains of four, eight, 16, or up to
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